Derivation of a robust mouse mammary organoid system for studying tissue dynamics

Author:

Jamieson Paul R.12,Dekkers Johanna F.12,Rios Anne C.12,Fu Nai Yang12,Lindeman Geoffrey J.134,Visvader Jane E.12ORCID

Affiliation:

1. Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia

2. Department of Medical Biology, The University of Melbourne, Parkville, VIC 3010, Australia

3. Familial Cancer Centre and Department of Medical Oncology, The Royal Melbourne Hospital, Parkville, VIC 3050, Australia

4. Department of Medicine, The University of Melbourne, Parkville, VIC 3010, Australia

Abstract

Advances in stem cell research have enabled the generation of mini-organs or organoids that recapitulate phenotypic traits of the original biological specimen. Although organoids have been demonstrated for multiple organ systems, there are more limited options for studying mouse mammary gland formation in vitro. Here we have built upon previously described culture assays to define culture conditions that enable the efficient generation of clonal organoid structures from single-sorted basal mammary epithelial cells (MECs). Analysis of Confetti-reporter mice revealed the formation of uni-coloured structures and thus the clonal nature of these organoids. High resolution 3D imaging demonstrated that basal cell-derived, complex organoids comprised an inner compartment of polarized luminal cells with milk-producing capacity and an outer network of elongated myoepithelial cells. Conversely, structures generated from luminal MECs rarely contained basal/myoepithelial cells. Moreover, flow cytometry and 3D microscopy of organoids generated from lineage-specific reporter mice established the bipotent capacity of basal cells and the restricted potential of luminal cells. In summary, we describe optimized in vitro conditions for the efficient generation of mouse mammary organoids that recapitulate features of mammary tissue architecture and function, and can be applied to understand tissue dynamics and cell-fate decisions.

Funder

National Health and Medical Research Council

Australian Cancer Research Foundation

National Breast Cancer Foundation

European Commission

Victorian Cancer Agency

Publisher

The Company of Biologists

Subject

Developmental Biology,Molecular Biology

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